Ludwig Institute for Cancer Research, University of Oxford, Oxford, OX3 7DQ, United Kingdom.
Cold Spring Harb Perspect Biol. 2010 May;2(5):a001032. doi: 10.1101/cshperspect.a001032. Epub 2009 Dec 9.
The p53 tumor suppressor pathway is central both in reducing cancer frequency in vertebrates and in mediating the response of commonly used cancer therapies. This article aims to summarize and discuss a large body of evidence suggesting that the p53 pathway harbors functional inherited single-nucleotide polymorphisms (SNPs) that affect p53 signaling in cells, resulting in differences in cancer risk and clinical outcome in humans. The insights gained through these studies into how the functional p53 pathway SNPs could help in the tailoring of cancer therapies to the individual are discussed. Moreover, recent work is discussed that suggests that many more functional p53 pathway SNPs are yet to be fully characterized and that a thorough analysis of the functional human genetics of this important tumor suppressor pathway is required.
p53 肿瘤抑制途径在降低脊椎动物的癌症发病率和介导常用癌症疗法的反应方面都具有核心作用。本文旨在总结和讨论大量证据，这些证据表明 p53 途径具有功能性遗传单核苷酸多态性（SNPs），这些 SNPs 会影响细胞中的 p53 信号转导，从而导致人类癌症风险和临床结果的差异。本文还讨论了通过这些研究获得的有关如何针对个体定制癌症疗法的功能性 p53 途径 SNPs 的见解。此外，还讨论了最近的工作，这些工作表明，还有许多更多的功能性 p53 途径 SNPs 有待充分表征，并且需要对这个重要的肿瘤抑制途径的功能性人类遗传学进行全面分析。
